The regulation and function of p21ras in signal transduction by the T cell antigen receptor

Abstract

T lymphocyte activation is initiated by triggering of the T cell antigen receptor (TCR). The TCR is a multichain complex comprising a disulfide-linked heterodimer of the idiotypic αβ chains noncovalently associated with a signal transduction complex composed of the invariant CD3 γ, δ, ϵ chains and the ζ (16 kDa) and η (22 kDa) subunits. The cytoplasmic domains of the CD3 and ζ subunits are crucial for TCR coupling to intracellular PTKs which is absolutely required for all subsequent T cell responses. PTKs are known to couple the TCR to an inositol lipid specific phospholipase C, PLCγ1 thus enabling the TCR to regulate the hydrolysis of membrane phosphoinositides (PtdIns), in particular phosphatidylinositol (4,5)-biphosphate (PtdIns(4,5P2), liberating inositol (1,4,5)-triphosphate(Ins(1,4,5)P3) and 1,2-diacylglycerol (DAG). Ins(1,4,5)P3 releases Ca2+ from the endoplasmic reticulum which results in an initial rapid rise in the concentration of intracellular Ca2+; DAG is known to activate the serine/threonin kinase, protein kinase C (PKC).